6586 Organometallics, Vol. 28, No. 22, 2009
Yi and Gao
their synthetic potential has not been fully exploited in part
because the catalytic method typically produces a mixture of
gem- and (E)/(Z)-enol ester products.10 Considerable re-
search has been devoted to control both regio- and stereo-
selectivity of the enol ester products by modulating the steric
and electronic nature of the metal catalysts. Generally, late
transition metal catalysts have been found to be effective for
producing a mixture of (E)- and (Z)-enol esters from anti-
Markovnikov addition of carboxylic acids to terminal al-
kynes over gem-enol ester products,10,11 though the regiose-
lective formation of gem-enol esters has been achieved by
using Ru and Rh catalysts.12 Dixneuf and co-workers ele-
gantly showed the relationship between steric environment
of the ruthenium-phosphine catalysts and the stereoselective
formation of the (Z)-enol esters.13 In a subsequent study, the
same authors reported a regioselective 2:1 alkyne-to-car-
boxylic acid coupling reaction to form the dienyl esters by
using the Cp*Ru(COD)Cl catalyst, in which a ruthenacy-
clopentadiene complex was proposed as the key intermediate
species for the coupling reaction.14 Both intra- and inter-
molecular versions of the catalytic alkyne-to-carboxylic
coupling methods have been successfully applied to the
synthesis of complex organic molecules.15 Despite consider-
able synthetic and mechanistic progress, however, neither
the nature of reactive intermediate species nor controlling
factors for the formation of gem- vs (E)/(Z)-enol esters have
been clearly established.
We previously reported that the coordinatively unsatu-
rated ruthenium-hydride complex (PCy3)2(CO)RuHCl (1) is
a highly effective catalyst for the coupling reactions of
alkenes and alkynes.16 Both ruthenium-acetylide and -viny-
lidene complexes have been found to be the key species for
these coupling reactions.17 As part of ongoing efforts to
extend synthetic utility of the ruthenium-catalyzed alkyne
coupling reactions, we have been exploring the catalytic
activity of the ruthenium-hydride complexes toward the
coupling reactions of alkynes with heteroatom substrates.
In this article, we report a detailed scope and mechanistic
study of the ruthenium-catalyzed alkyne-to-carboxylic acid
coupling reaction, which provides new insights in mediating
solvent-controlled regio- and stereoselective formation of
the enol ester products.
Results and Discussion
Catalyst Survey and Reaction Scope. The catalytic activity
of selected ruthenium complexes was initially screened for
the coupling reaction of benzoic acid and 4-ethynylanisole
(eq 1). Among the selected ruthenium catalysts, complex 1
was found to exhibit uniquely high catalytic activity and
selectivity in giving the gem-enol ester product 2a within 5 h
at 95 °C in CH2Cl2 (Table 1). Both Ru3(CO)12 and Cp*Ru-
(PPh3)2Cl showed significant activity, but suffered from low
selectivity in forming the coupling products. The catalyst
Cp*Ru(COD)Cl, on the other hand, produced a mixture of
1:1 and 1:2 coupling products, which is in line with the
previously reported results on the formation of dienyl ester
products.14
Next, the solvent effect on the activity and selectivity
patterns of the catalyst was examined for the coupling
reaction of benzoic acid and 4-ethynylanisole (Table 2). A
remarkably strong solvent influence on the ruthenium cata-
lyst 1 was observed in modulating the formation of the enol
ester products. Thus, the coupling reaction in relatively
nonpolar and noncoordinating solvents tended to favor the
formation of geminal coupling product 2a over (E)- and (Z)-
3a, of which CH2Cl2 was found to be the best in producing
the geminal product 2a among these solvents (entry 4). In
contrast, among polar coordinating solvents, which tended
to favor the formation of (Z)-enol ester product (Z)-3a, THF
was found to be the most selective in giving (Z)-3a (entry 10).
It should be emphasized that the formation of 1:2 coupling
products was not observed from the coupling reaction
catalyzed by 1. Other ruthenium catalysts such as Ru3-
(CO)12, Cp*Ru(PPh3)2Cl, and Cp*Ru(COD)Cl surveyed in
Table 1 did not exhibit a similar degree of solvent control in
forming the coupling products.
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44, 103–106. (e) Hua, R.; Tian, X. J. Org. Chem. 2004, 69, 5782–5784. (f)
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It is imperative to briefly mention the recent advances in
using solvents with different polarity and coordinating abil-
ity to control the product selectivity. Coordinatively unsa-
turated transition metal complexes have been found to be
particularly sensitive to the nature of solvents in mediating
unreactive bond activation reactions.18-20 For example,
ꢀ
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^
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